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Introduction: Type 2 diabetes mellitus (T2DM) is a significant risk factor for the development of critical limb ischemia (CLI), the most advanced stage of peripheral arterial disease. The concurrent existence of T2DM and CLI often leads to adverse outcomes, namely limb amputation. Objective: To identify biomarkers for improving the screening of CLI in high-risk people with T2DM. Methods: We investigated metabolome profiles in serum samples of 113 T2DM people with CLI (n = 23, G2) and without CLI (n = 45, G0: no lower limb stenosis (LLS) and n = 45, G1: LLS < 50%), using hydrogen nuclear magnetic resonance (1H NMR) approach. Principle component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to analyze 1H NMR data. Results: Twenty potential metabolites that could discriminate people with T2DM and CLI (G2) from non-CLI patients without LLS (G0) were determined in serum samples. The correct percent of classification for the PLS-DA model for the test set samples was 85% (n = 20) and 100% (n = 5) for G0 and G2 groups, respectively. Non-CLI patients with LLS < 50% (G1) were projected on the PCA abstract space built using 20 discriminatory metabolites. Eleven people with T2DM and LLS < 50% were prospectively followed, and their ankle-brachial index (ABI) was measured after 4 years. A promising agreement existed between the PCA model's predictions and those obtained by ABI values. Conclusion: The findings suggest that confirmation of blood potential metabolic biomarkers as a complement to ABI for screening of CLI in a large group of high-risk people with T2DM is needed. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis is the leading cause of death in patients with diabetes. We aimed to evaluate the association between ankle-brachial index (ABI) and toe-brachial index (TBI) with carotid intima-media thickness (CIMT) in patients with type 2 diabetes (T2DM). Methods: This cross sectional study included 296 patients with T2DM who met the American Diabetes Association criteria for the assessment of peripheral arterial atherosclerosis. The ABI ≤ 0.9 and TBI ≤ 0.7 were considered as abnormal values. Linear and logistic regression analyses were performed to evaluate the association between TBI/ABI and CIMT. Results: Right CIMT was significantly greater in the low TBI group (p = 0.03) while, left CIMT did not show a significant difference. Each 0.1-unit decrease in TBI value was independently associated with 0.017 mm increase in the right CIMT (β ± SE; -0.017 ± 0.005, p = 0.002) and with odds of the presence of increased CIMT [odds ratio and 95% confidence interval: 1.21 (1.02, 1.44)] after adjustment with all traditional risk factors. There was not any significant association between ABI and increased CIMT. Conclusions: Beyond a suitable tool for the diagnosis of peripheral artery disease in patients with T2DM, TBI can be applied for prediction of subclinical carotid atherosclerosis. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the efficacy of empagliflozin compared to pioglitazone in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM). Methods: In this prospective randomized, double-blind, placebo-controlled trial, we assigned 106 patients with NAFLD and T2DM to receive empagliflozin 10 mg (n = 35), pioglitazone 30 mg (n = 34), or placebo (n = 37) for 24 weeks. Liver fat content and liver stiffness were measured using fibroscans. Body composition assessment was performed by dual-energy x-ray absorptiometry (DEXA) scans. The primary end point was change from baseline in liver steatosis, using the controlled attenuation parameter (CAP) score. Results: A borderline significant decrease in CAP score was observed with empagliflozin compared to placebo, mean difference: − 29.6 dB/m (− 39.5 to − 19.6) versus − 16.4 dB/m (− 25.0 to − 7.8), respectively; p = 0.05. Using multivariate analysis, we observed a significant reduction in the placebo-corrected change in liver stiffness measurement (LSM) with empagliflozin compared to pioglitazone: − 0.77 kPa (− 1.45, − 0.09), p = 0.02, versus 0.01 kPa (95% CI − 0.70, 0.71, p = 0.98), p for comparison = 0.03. Changes in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), fasting insulin, homeostatic model assessment for insulin resistance (HOMA-IR), HOMA2-IR, fibrosis-4 index (FIB4 index), NAFLD fibrosis score, aspartate aminotransferase to platelet ratio index (APRI), android/gynecoid ratio (A/G ratio), and skeletal muscle index (SMI) were comparable between the two treatment groups, while significant reductions of the body weight and visceral fat area were observed only in the empagliflozin group (p < 0.001 and p = 0.01, respectively) and both were increased in the placebo and pioglitazone groups. There were no serious adverse events in either group. Conclusion: Treatment for 24 weeks with empagliflozin, in contrast to pioglitazone, was associated with improvement of liver steatosis and fibrosis in patients with NAFLD and T2DM. In addition, body weight and abdominal fat area were decreased in the empagliflozin group. Trial Registration: Iranian Registry of Clinical Trials (IRCT), IRCT20190122042450N3. [ABSTRACT FROM AUTHOR]

Undesired effects of synthetic antidiabetic agents have made researchers to seek for safer and healthier resources. With this aspect, herbal materials have attracted substantial research interest and are being extensively investigated. Considering that herb-drug interactions can be a double-edged sword presenting both risks and benefits, investigation of such interactions is greatly in demand. to investigate possible beneficial effects of hydroalcoholic extract of Securigera Securidaca seed (HESS) on antioxidant capacity, fibroblast growth factor 21 (FGF21) and insulin resistance in Streptozotocin (STZ)-induced diabetic rats, alone and in combination with glibenclamide. Forty male Wistar rats were randomly divided in to eight equal groups including healthy and diabetic controls and six treated groups with a various doses of HESS alone and in combination with glibenclamide, for 35 consecutive days. Serum samples were taken and analyzed for biochemical profile, HOMA indexes, FGF21, oxidative/nitrosative stress and inflammatory biomarkers as compared with the controls. Moreover, total phenolic and flavonoid contents of herbal extract were assessed. The herbal extract was found to be rich in flavonoid and phenolic components. Both of glibenclamide and the HESS decreased glucose and insulin resistance, as well as increased body weight and insulin sensitivity. Moreover, the extract could mitigate oxidative/nitrosative stress and inflammation dose-dependently, however, the standard drug was less effective than HESS. Induction of diabetes increased FGF21 levels and both of the treatments could reduce its contents, however, glibenclamide was more effective than HESS. The results clearly show that there is no contradiction between HESS and glibenclamide. Moreover, the herbal extract could augment antioxidant and anti-inflammatory properties of the standard drug. Image 1 [ABSTRACT FROM AUTHOR]